title: Mice with gene targetted prion protein alterations show that Prnp, Sinc and Prni are congruent.
abstract: Classical genetic analysis has identified Sinc/Prni as the major gene controlling mouse scrapie incubation time. Sinc/Prni is linked to Prnp, the gene encoding the prion protein (PrP). Prnp alleles express distinct PrP protein variants, PrP A and PrP B, which arise from codon 108L/F and 189 T/V dimorphisms. Prnp genotype segregates with incubation time length which suggests, but does not prove, that incubation time is controlled by PrP dimorphisms, and that the Sinc/Prni and Prnp loci are congruent. We have used gene targetting to construct mice in which the endogenous Prnp allele has been modified to express PrP B instead of PrP A. Challenge with a mouse-adapted BSE strain results in dramatically shortened incubation times and demonstrates that PrP dimorphisms at codon 108 and/or 189 control incubation time, and that Sinc/Prni and Prnp are congruent.
authors.affiliation: Institute of Cell and Molecular Biology, University of Edinburgh, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Moore
authors.forename: J
authors.initials: J
authors.lastname: Hope
authors.forename: P A
authors.initials: PA
authors.lastname: McBride
authors.forename: I
authors.initials: I
authors.lastname: McConnell
authors.forename: J
authors.initials: J
authors.lastname: Selfridge
authors.forename: D W
authors.initials: DW
authors.lastname: Melton
authors.forename: J C
authors.initials: JC
authors.lastname: Manson
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003062:Codon; D014644:Genetic Variation; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017354:Point Mutation; D011328:Prions / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D012608:Scrapie / Q000235:genetics / Q000473:pathology; D013045:Species Specificity
chemical_list: D003062:Codon; D011328:Prions